National Cancer Center Japan (Headquarters: Chuo-ku, Tokyo; President: Hitoshi Nakagama; hereafter, 'National Cancer Center'), Shonai Regional Industry Promotion Center (Headquarters: Tsuruoka City, Yamagata Prefecture; President: Osamu Minakawa) and Sumitomo Dainippon Pharma Co., Ltd. (Head Office: Osaka; Representative Director, President and CEO: Hiroshi Nomura; hereafter, 'Sumitomo Dainippon Pharma') have conducted a collaborative research on the search of biomarker candidates and applicable disease subtypes for DSP-5336 (Development code; hereafter, 'the compound'), a novel MENIN-MLL interaction inhibitor. We announce that the first patient has been administered with the compound in the Phase 1/2 clinical study that Sumitomo Dainippon Pharma is conducting in US, Canada, and Japan for acute myeloid leukemia.
Chemotherapy continues to be the major treatment for acute leukemia to date. But there are some cases with an unfavorable prognosis where a cure is difficult to be achieved. In particular, the 5-year survival rate for the acute leukemia patients with chromosomal translocations of the MLL gene is extremely poor (less than 20%), and thus there is a great need for the development of innovative molecularly targeted therapies.
Chromosomal translocations of MLL generate MLL fusion genes, whose products induce abnormally high expression of some leukemia-associated genes, causing malignant leukemia. The research team of National Cancer Center Tsuruoka Metabolomics Laboratory at Shonai Regional Industry Promotion Center led by Akihiko Yokoyama was the first in the world to discover that the onset of acute leukemia involved association of MLL fusion protein with a co-factor protein called MENIN. This provided a basis on which compounds that disrupt MLL-MENIN protein interaction would have inhibitory effects on leukemia cell growth. Based on this notion, the compound, a selective, potent inhibitor of MENIN-MLL interaction, was developed in the collaborative research project (DSK project) between Yokoyama's research team then in Kyoto University (Headquarters: Kyoto; President: Nagahiro Minato) and Sumitomo Dainippon Pharma. In addition, the team of Issay Kitabayashi at National Cancer Center, and the Yokoyama's team then in National Cancer Center Tsuruoka Metabolomics laboratory performed nonclinical studies (hereafter, 'the studies*') for the compound, demonstrating an excellent antitumor activity of the compound against various types of leukemia using human clinical specimens accumulated by the National Cancer Center as well as various mouse leukemia models.
Sumitomo Dainippon Pharma will continue to develop the compound as an anti-cancer drug, aiming to apply for the patients with the acute myeloid leukemia with MLL gene rearrangements or with NPM1 mutations. Leveraging the knowledge of cancer research accumulated in the National Cancer Center and the knowledge of drug discovery research accumulated in Sumitomo Dainippon Pharma, they aimed to deliver innovative therapies to acute myeloid leukemia patients with an unfavorable prognosis.
The studies are supported by Japan Agency for Medical Research and Development (AMED) for the basic scheme of its Acceleration Transformative Research for Medical Innovation Program (ACT-M) (collaboration among industry, academia and government). The National Cancer Center is also supported by an AMED Project for Cancer Research and Therapeutic Evolution (P-CREATE) for related blood cancer research.
About acute myeloid leukemia
Acute myeloid leukemia, a type of blood cancer, is caused by overgrowth of myeloid-type blood cells (leukemia cells) with impaired differentiation capability in the bone marrow where the most blood cells are produced. It is a fatal disease that causes severe symptoms in a short period of time if appropriate treatment is not given, because abnormal proliferation of leukemia cells inhibits normal hematopoietic function. Around 7,000 people are diagnosed with this disease in Japan annually. In recent years, more sophisticated disease type classification based on chromosomal karyotype/gene mutation analysis of leukemia cells has helped determine treatment strategies suitable for each patient. Although potent anticancer agents (chemotherapy) are used as the primary treatment option for acute myeloid leukemia, the patients with treatment-resistant type disease and the elderly patients who cannot endure such a strong treatment, do not have sufficient treatment options.
About National Cancer Center
The National Cancer Center is one of the largest cancer research institutes in Japan. We support a wide range of activities from extremely original basic research to research on the development of actual therapeutic and diagnostic agents in cooperation with the National Cancer Center Hospital (Tokyo) and National Cancer Center Hospital East (Chiba). So far, we have achieved many results in cancer genome analysis by developing various sequencers and unique bioinformatics, which has led to drug development based on the discovery and clinical studies in collaboration with the hospitals. We are also focusing on the development of elemental technologies for cancer genomic medicine. We are working on the development of Japan's first oncogene panel test and its insurance coverage, and a gene panel test method for hematopoietic malignancies and pediatric cancers. Furthermore, in expanding bioresources, more than 400 types of patient-derived xenograft mice and more than 20,000 types of fresh frozen tumor tissue biobanks have already been established, and these can be effectively utilized in Japan. We are developing joint research with outside academia and companies.
About Shonai Regional Industry Promotion Center
Shonai Regional Industry Promotion Center was established in 1987 as a public foundation with the objectives of creating vibrant regional economies and communities and contributing to improve the lives of local people by fostering and supporting the development of local industry. This is the organization responsible for implementing the projects of the National Cancer Center Tsuruoka Metabolomics Laboratory.
About Sumitomo Dainippon Pharma
Sumitomo Dainippon Pharma defines its corporate mission as to 'broadly contribute to society through value creation based on innovative research and development activities for the betterment of healthcare and fuller lives of people worldwide'. By channeling our total efforts into research and development for new drugs, we aim to provide innovative and effective pharmaceutical solutions to people not only in Japan but also worldwide in order to realize our corporate mission.
Contact:
TEL: 81-3-3542-2511
Email: ncc-admin@ncc.go.jp
SUMITOMO PHARMA CO., LTD. 
